RESUMEN

The binding constants for racemic, R and S naproxen and ibuprofen to human serum albumin have been determined by a circular dichroic technique. The ibuprofens and naproxens show no measurable extrinsic optical activity on interaction with the protein, and so the extrinsic Cotton effect shown following the diazepam-albumin interaction is used as a probe. The presence of the drugs reduce the amount of diazepam bound as shown by the interaction is used as a probe. The presence of the drugs reduce the amount of diazepam bound as shown by the reduced size of the induced ellipticity. The calculated primary binding constants show that the S form of both drugs bind to the albumin more tightly than the R form and that the racemic forms bind less tightly than either enantiomer.

Asunto(s)

RESUMEN

PURPOSE: The heats of reaction between the enantiomers and racemates of ibuprofen and naproxen and human serum albumin (HSA) are to be measured with and without the addition of octanoic acid. The effects of octanoic acid on the free energies of interaction between the drugs and HSA is to be determined and compared to that estimated from theoretical equations. METHODS: The heats of reaction have been measured directly by flow microcalorimetry. RESULTS: The data showed that octanoic acid lowered the 1:1 binding constants for all the drug-HSA interactions investigated. The effect of octanoic acid was greater on the R than on the S forms of the drugs as shown by the differences in free energies of interaction in the presence and absence of octanoic acid. CONCLUSIONS: The increased free energy differences for the binding of the enantiomers of both drugs to HSA in the presence of octanoic acid is closer to the value deemed to be necessary for the separation of enantiomers by Davenkov, and shows the importance of the addition of octanoic acid to the mobile phase in the separation of these enantiomers on immobilized albumin columns.

Asunto(s)

RESUMEN

PIP: By the mid-1990s, global human immunodeficiency virus (HIV) infections among women are expected to equal those among men. This trend reflects economic, political, and cultural factors that limit women's ability to protect themselves from HIV transmission. Studies in developing countries have indicated that HIV-infected women (other than sex workers) do not average significantly more sex partners than uninfected controls; the chief risk factors are poverty, migration to urban centers for employment as domestics, and sexual contact with soldiers or truck drivers. Social marketing projects aimed at increasing condom availability overlook the fact that, in many cultures, fidelity is confirmed by having sex without a condom. The same social forces that place poor women at greater risk of HIV infection are responsible for the inadequate allocation of resources to assist women with HIV and those who serve as caretakers of infected family members. The articles in this monograph illustrate the interaction of acquired immunodeficiency syndrome (AIDS), gender, and poverty in North America and on a global level.^ieng

Asunto(s)

RESUMEN

The degradations of 13-cis-retinoic acid and all-trans-retinoic acid in an organic solvent were determined with an HPLC assay. The degradation curves at 70, 50 and 37 degrees C all showed autocatalytic characteristics for both isomers. For this kind of complex reaction, the usual method cannot be used to estimate the shelf-lives and half-lives at room temperature. In this work a new method was developed to directly calculate the shelf-lives and half-lives. From this equation the activation energy was found to change as the multiple step reaction progressed.

Asunto(s)

RESUMEN

A novel air-gap enzyme electrode was developed by amalgamating the principles controlling ion-selective electrodes, enzyme kinetics, and diffusion of molecules across membranes. Commercially available ammonia and carbon dioxide gas-sensing electrodes were modified to measure the respective gases over a head-space. A plexiglass cell was designed and fabricated to house the modified electrodes. The air-gap electrodes exhibited superior sensitivity and response characteristics compared to the original membrane electrodes. The plexiglass cell was divided into two compartments by virtue of a selectively permeable membrane. Enzymatic reactions were conducted in the cell to determine quantitatively the concentration of the substrate. L-Phenylalanine ammonia lyase was used to determine L-phenylalanine with the ammonia electrode and L-glutamate decarboxylase was utilized for the determination of L-glutamic acid by the carbon dioxide electrode. Near-Nernstian slopes were obtained for the response of the enzyme electrodes. In addition to the good reproducibility, the method provided unique ability to reuse the same enzyme solution for several determinations of various concentrations of the analyte. The performance of the two compartment cell and air-gap enzyme electrode was found to be superior in comparison to conventional enzyme electrodes.

Asunto(s)

Asunto(s)

RESUMEN

The distribution of chlorpromazine (CPZ) between aqueous buffer solutions and 1-octanol was studied over a wide range of pH, buffer concentration, and temperature. A mathematical model was developed to simulate the distribution profiles. It is assumed that only monomers of CPZ exist in the organic phase, whereas in the aqueous phase, association equilibria were assumed to occur. The model predicted the formation of dimers and no higher aggregates over most of the concentration range covered in this study. Thermodynamic parameters for the partition equilibria were evaluated from the equilibrium partition coefficients measured as a function of temperature. Positive values of delta H and delta S were obtained for the transfer of CPZ from the aqueous to the organic phase. The process is entropy controlled indicative of a hydrophobic interaction between CPZ and the aqueous solvent.

Asunto(s)

RESUMEN

In a study aimed at the development of a long-acting insulin preparation, Manallack and co-workers (5) reported on the design of small organic molecules which have the potential to bind to insulin and stabilize its hexameric aggregate. Two of the molecules that were designed with their computer graphics program were thought to be particularly promising as ligands: benzene-p-disulfonate and benzene-p-diphosphonate. In the present work, the insulin binding abilities of these molecules have been thoroughly tested. A theoretical binding program, GRID, was used to calculate the binding energetics of the molecules and to predict the most probable site of their binding. Microcalorimetry and NMR line broadening techniques were used to measure the actual binding reactions of the ligands. For both compounds, no evidence of binding to insulin was ever observed in either the microcalorimetry or the NMR studies. In contrast, a series of phenolic ligands commonly used as preservatives for insulin showed evidence of substantial binding using either method. An explanation has been proposed for this apparent discrepancy between computer predictions and actual experimental data: The theoretical programs do not take solvation effects of the aqueous medium into account. Solvation effects would tend to inhibit binding of the ionized ligand molecules due to charge delocalization and steric crowding.

Asunto(s)

RESUMEN

Flow microcalorimetry was used to measure the free energies, enthalpies, and entropies of interactions between the hormone insulin and small ligand molecules or ions. Measurable amounts of heat were obtained for binding of four phenolic preservative molecules--phenol, meta-cresol, resorcinol, and methylparaben--to both two-zinc and zinc-free insulin and for binding of zinc ions to zinc-free insulin. All of the reactions were spontaneous, but the phenolic binding was driven by enthalpy, while that of zinc was entropy-driven. A combination of van der Waals interactions, hydrophobic effects, and protein conformational changes appeared to be involved in binding of the phenolic ligands. Zinc ions displayed two types of binding to insulin, both involving ion-dipole interactions.

Asunto(s)

RESUMEN

The development of a prototype ion-selective microelectrode for bile salts is described. The microelectrodes demonstrated Nernstian response (59 +/- 10 mV dec-1) with sodium deoxycholate in Tris (0.2 M, pH 9.0, 15-30 degrees C), HEPES (0.13 M, pH 7.5), and bicarbonate buffers (0.1 M, pH 7.5) (25 +/- 0.1 degrees C) were stable for several days, and the responses were highly reproducible. The microelectrodes were selective for bile salts over the physiologically important inorganic anions, bicarbonate and chloride. The response to sodium cholate (42 mV dec-1) was consistently lower than the ideal response (59 mV dec-1). This ion-selective microelectrode may show promise as a useful tool for the determination of intracellular bile salt activity.

Asunto(s)

Asunto(s)

RESUMEN

The binding of Ca2+ to micelles of glycine and taurine bile acid conjugates was studied using a Ca2+-specific electrode. An investigation of the effect of buffer concentration, pH, added electrolyte and lecithin was also performed. The results indicate that the binding of Ca2+ to bile salt micelles is dependent on the number of hydroxyl groups on the steroid nucleus and on the nature of the head conjugating group, namely, glycine or taurine. It is speculated that the binding of Ca2+ to bile salt micelles may act as one mechanism to lower Ca2+ activity in bile and, thus, reduce its tendency to precipitate as insoluble calcium salts and further growth into gallstones.

Asunto(s)

RESUMEN

The kinetics of dissolution of dispersions of egg phosphatidylcholine (lecithin) by bile salts was studied by observing the decrease in turbidity as mixed micelles of lecithin and bile salts were formed. The rate of dissolution of lecithin corresponding to formation of mixed micelles was studied in the presence of dihydroxy bile salts, sodium deoxycholate, sodium chenodeoxycholate, sodium ursodeoxycholate and one trihydroxy bile salt, sodium cholate. The rate of dissolution of lecithin and mixed micelle formation decreased in the order: chenodeoxycholate greater than deoxycholate greater than cholate greater than ursodeoxycholate. Kinetic solvent isotope studies in D2O, along with measurement of enthalpies of mixed micelle formation both in H2O and D2O, suggest that formation and stabilization of mixed micelles are related to "hydrophobicity" as estimated by high performance liquid chromatography retention factors.

Asunto(s)

RESUMEN

The problem of differentiating primary bone tumors from subacute osteomyelitis was reviewed in 15 typical cases. Presenting symptoms, duration of illness, admitting laboratory data, and location of the pathologic condition were of little assistance in diagnosis. Preoperative diagnoses included benign and malignant neoplasms as well as osteomyelitis. In all cases the final diagnosis of subacute osteomyelitis was made only after open biopsy. Surgical curettage combined with appropriate antibiotic therapy was deemed essential for adequate treatment of this infectious process. Drug therapy included three to six weeks of parenteral antibiotics followed by three to six weeks of oral antibiotics. The protocol for duration of antibiotic therapy was based on the type of bacteria, the antibiotic serum levels achievable via the oral route, and patient compliance.

Asunto(s)

RESUMEN

The kinetics of dissolution of dispersions of egg phosphatidylcholine (lecithin) by bile salts was studied by observing the decrease in turbidity as mixed micelles of lecithin and bile salt were formed. The rate of dissolution of lecithin corresponding to the formation of mixed micelles was studied in the presence of dihydroxy bile salts, sodium deoxycholate, sodium chenodeoxycholate, sodium ursodeoxycholate, and one trihydroxy bile salt, sodium cholate. The rate of dissolution of lecithin and mixed micelle formation decreased in the order: chenodeoxycholate greater than deoxycholate greater than cholate greater than ursodeoxycholate. Kinetic solvent isotope studies in D2O, along with measurement of enthalpies of mixed micelle formation both in H2O and D2O, appear to indicate that the formation and stabilization of mixed micelles is related to "hydrophobicity" as estimated by high performance liquid chromatography retention factors.

Asunto(s)

Asunto(s)

RESUMEN

The ionophore antibiotic X-537A (lasalocid) transports biogenic amines across biological and artificial membranes. The major portion of amine flux (greater than 99%) occurs as a 1:1 neutral complex. The rank order of ionophore selectivity was determined for lipid bilayer membrane transport of amines based on a comparison of permeability coefficients: p-tyramine approximately beta-phenylethylamine approximately amphetamine greater than methamphetamine greater than dopamine greater than phenylephrine approximately metanephrine greater than norepinephrine greater than epinephrine. This rank order is in agreement with results obtained from partitioning measurements which were carried out in parallel to the bilayer membrane experiments. A correlation between amine structure and binding characteristics has been developed.

Asunto(s)

RESUMEN

Thirty-one postoperative fractures around the femoral component of previous total hip arthroplasties were reviewed retrospectively until healing occurred. This type of injury seemed to be associated with either high-velocity trauma or weakening of bony stock secondary to stress risers from prior surgery or loosening. These fractures were classified as Type A at the stem tip, Type B spiralling around the stem, and Type C comminuted around the stem. Type A fractures have a significant incidence of nonunion in the face of multiple previous proximal femoral surgeries, but, after healing, usually show no loosening. Type B fractures usually will heal without operative intervention but have a high incidence of associated eventual component loosening. Type C fractures need immediate surgery to allow mobilization of the elderly patient. When postfracture revision surgery with long-stem component or plating is required, the technical order of priority should be adequate bony apposition of fracture fragments, good cement technique at the proximal femur, bone grafting.

Asunto(s)

RESUMEN

The distribution of four bile salts: sodium cholate (I), sodium deoxycholate (II), sodium chenodeoxycholate (III), and sodium ursodeoxycholate (IV), between aqueous buffer and 1-octanol has been measured as a function of temperature between 25 and 55 degrees and as a function of bile salt concentration at concentrations less than 0.1 mole/liter in the aqueous phase. The distribution isotherms obtained have been explained on the basis of reversible association in the aqueous phase. The treatment assumes that the bile acid exists as a monomer in the organic phase, which is verified by vapor pressure osmometry. A graphical method has been employed to estimate the association constants in the aqueous phase for the various equilibria encountered. An aggregation number of four for IV and 12 for I, II, and III has been estimated. From the results, thermodynamic functions associated with the transfer of each of the bile salts from water to octanol and those associated with association processes in the aqueous phase were calculated. These results are consistent with previous findings that the premicellar association of bile salts occurs by hydrophobic interaction. The thermodynamics of transfer of bile salts revealed an unfavorable enthalpic and favorable entropic contribution for all four bile salts. However, for IV, which is an epimer of III, both enthalpic and entropic contributions are reduced, compared to III, suggesting a pronounced effect of stereochemical orientation on hydrophobic interaction.

Asunto(s)

RESUMEN

The distribution of deoxycholic acid (I) between aqueous buffer and an organic phase consisting of isooctane-1-octanol (70:30, v/v) (System A) or isooctane-chloroform (80:20, v/v) (System B) was studied. The distribution isotherms suggested that I associates strongly in the organic Systems A and B unlike in pure 1-octanol. Therefore, a previous model, describing distribution of bile salts between 1-octanol and aqueous buffer, was modified to include association of I in the organic phases to describe distribution behavior. The treatment suggested that I exists as monomer and dimer in System A with a dimerization constant of 820 M-1. A model consisting of monomer-tetramer-hexamer in the organic phase best describes the data for System B. The data support the view that association in the organic phase is due to hydrogen bonding between bile acid molecules.

Asunto(s)